Our major effort will be directed toward elucidating the acute and chronic effects of ethanol (and other potential "teratogens") on placental function. The aim is to determine whether ethanol, acetaldehyde, caffeine and nicotine impair the delivery of selected nutrients to the fetus and whether this may explain (at least in part) the fetal-alcohol syndrome in man and its variants in the experimental animal. To assess this, studies will be carried out in vitro with rat placental fragments, human placental fragments and its vesicles, choriocarcinoma cells in tissue culture and in vivo in pregnant rats and sheep. In vitro, various concetrations of ethanol, acetaldehyde, caffeine, nicotine and benzodiazepines will be added singly or together, and the effects of these on placental uptake of selected amino acids and other nutrients will be assessed. In vivo, the rats and sheep will be exposed to ethanol acutely or chronically, and the effects of such exposure will be determined on placenta studied subsequently in vitro. In other in vivo studies, transfer of the nutrients to the fetus will be measured. From these composite observations, we hope to determine whether ethanol or its derivatives and other agents exert fetotoxic effects by impairing placental function.